Lecture Three: Leading Causes of Mortality, Ages 15-44 Biomedical Engineering for Global Health.

Lecture Three:Leading Causes of Mortality, Ages

15-44

Biomedical Engineering for Global Health

Review of Lecture Two:Leading Causes of Mortality, Birth-

Age 4 Developing world

1. Perinatal conditions2. Lower respiratory infections3. Diarrheal diseases4. Malaria

Developed world1. Perinatal conditions2. Congenital anomalies3. Lower respiratory infections4. Unintentional injuries

Ratio of Mortality Rate

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WHO. Mortality: Revised Global Burden of Disease (2002)

1. Perinatal Conditions

Question: What is the #1 way to prevent septicemia in a newborn in the developing world?

2. Lower Respiratory Infections

Question: How can a busy health worker (or a parent) quickly screen for pneumonia in a child?

3. Diarrheal Diseases Question: What is the #1 way to

prevent diarrheal illness in a newborn?

4. Malaria Question: How was malaria eradicated

from the southern U.S.? What are the challenges with implementing this technology in less developed countries?

Leading Causes of Mortality Ages 15-44

Developing World1. HIV/AIDS2. Unintentional injuries3. Cardiovascular diseases4. Tuberculosis

Developed World1. Unintentional injuries2. Cardiovascular diseases3. Cancer4. Self-inflicted injuries

1. HIV/AIDS

Burden of HIV/AIDS Pathophysiology of HIV Clinical course of HIV/AIDS Highly Active Antiretroviral Therapy Prevention of Mother to Child

Transmission (PMTCT)

Burden of HIV/AIDS Worldwide

33.2 million people are living with HIV/AIDS 20 million people have been killed by the

disease 2007:

2.1 million deaths 2.5 million new HIV infections 17% of new infections occurred in children (<15

yrs) 2/3 of those with AIDS and 3/4 of all AIDS

deaths are in sub-Saharan Africa 6800 new infections per day

96% in low- and middle-income countries 1200 children

Source: 2007 AIDS Epidemic Update, UNAIDS/WHO

AIDS has Reduced Life Expectancy

Beaglehole R, Irwin A, Prentice T. The World Health Report 2004: Changing History.

Burden of HIV/AIDS in the U.S.

1.2 million people have HIV/AIDS (prevalence) 30,000-40,000 new infections per year

(incidence) Only 7 countries in the world have more

people living with HIV than the U.S. Routes of transmission:

Unsafe sex between men (53%) Unprotected heterosexual intercourse (32%) Non-sterile drug injection equipment (18%)


Burden of HIV/AIDS in the U.S.

Racial and ethnic minorities are disproportionately affected: 48% of AIDS diagnoses are African-Americans (15%

pop) The rate of new HIV diagnoses was 21x higher in

African-American women than in Caucasian women Women are increasingly affected:

The proportion of women among new HIV/AIDS diagnoses have risen from 15% to 26% in 10 years

Question: Why is the prevalence of HIV in the U.S. continuing to increase?


Pathophysiology of HIV/AIDS

Michael W. Davidson at Florida State University

Pathophysiology of HIV/AIDS

Roche

Clinical Course of HIV/AIDS

Pantaleo, G., Graziosi, C., Fauci, A. (1993) The Immunopathogenesis ofHuman Immunodeficiency Virus Infection. Mechanisms of Disease. 328 (S):327–335. c 1993. Massachusetts Medical Society. All rights reserved.

HIV/AIDS Therapy

Reverse Transcriptase Inhibitors (1987) Enzyme is specific to HIV Combinations of RTIs appear effective

HIV Protease Inhibitors (1995) HIV proteases are distinct from mammalian

proteases Most significant advance in HIV therapy yet

Highly Active Antiretroviral Therapy (HAART) Combination of three or more drugs

Fusion inhibitor (2003) Integrase inhibitor (2007) WHO World Report,

2004

HIV/AIDS Therapy HIV can rapidly mutate to quickly

develop resistance to a single drug Resistance develops much more

slowly to drug combinations Goal of HAART:

Reduce viral levels to undetectable levels

Has reduced death rate in US and Europe by 80%

The Lancet, Vol. 355, The CASCADE Collaboration, Survival after introduction of HAART in people with known duration of HIV-1 infection, page 1, 2000, with permission from Elsevier.

www.npr.org/templates/story/story.php?storyId=4724368

6 million people living with AIDS are in need of HAART. 90% are in just 34 developing countries

Prevention of Mother to Child Transmission (PMTCT)

3 routes of transmission: Parentally (during pregnancy) Perinatally (during delivery) Breast feeding (through milk)

4 Core interventions: HIV testing and counseling ARV prophylaxis (ZDV, NVP) Safer delivery practices Safer infant-feeding practices

Reduces transmission from 30-40% to 4-6%

Burden of Unintentional Injuries Accident Physics Slowed Driver Reaction Time Prevention of Road Accidents

2. Unintentional Injuries

Burden of Unintentional Injuries

More than 1.25 million people ages 15-44 die from unintentional injuries each year

1 million deaths in developing countries, 1/4 million in developed countries

40x this number are injured Major cause of disability Leading cause is road accidents:

500,000 deaths per year in this age group 90% of these deaths occur in developing

countries

Road Accidents in the U.S. Rates declining steadily A leading cause of potential years of life lost 2006:

42,642 Americans killed 2,699,000 Americans injured Fatal accident rates 3X higher for males than for

females Motorcycles: 40X higher death rate per mile

traveled 39% of fatalities related to alcohol use

Burden of Unintentional Injuries

Accident Physics

Newton’s 2nd Law: F = m a a = dv/dt a = initial velocity/time to come to rest

In a crash: Velocity slows to zero in a very short

time Generates large forces

How can we reduce these forces?1. Reduce initial velocity of impact2. Extend time that it takes passengers to

come to rest

CDC/Gwinnett Country Police Department.

Accident Physics1. Reduce initial velocity of impact

Excessive speed contributes to: 30% of deaths in developed countries 50% of deaths in developing countries

World Report on Road Traffic Injury Prebention, 2004

Slowed Driver Reaction Time

When drivers anticipate a crash, they have time to brake and reduce initial velocity

Factors which slow driver reaction time: Alcohol use Mobile phone use Poor visibility Driver inexperience


Alcohol impaired drivers have 17X increased risk of being in fatal crash

Alcohol use increases risk more in younger drivers

1 in 5 Americans will be involved in an alcohol-related crash at some time in their lives

TX BAC limit: 0.08+ g/dl is illegal Approx 3 drinks in a

140 lb individual Significant driving

impairment at just 0.04 BAC! World Report on Road Traffic Injury Prebention,

2004


Mobile phone use: At any given daylight moment in US:

10% of drivers are using a cell phone Increases driver reaction time by 0.5-1.5

seconds Risk of crash is 4X higher when using a mobile

phone Same as driving with a BAC of 0.09 g/ dl

4 states and D.C. have banned use of hand held phones while driving (NY, NJ, CT, CA) Partial bans in AR, AZ, FL, GA, IL, ME, MA, MN,

NH, NM, OH, PA, TN, VA, WA

Prevention of Road Accidents

2. Extending Time to Come to Rest: Crumple zones

Allow passengers additional time to decelerate

Seat belts Keep occupants in the passenger

compartment Stretch during impact Reduce risk of death in crash by 40-60%

Air bags When combined with seat belts, reduce risk

of serious and fatal injuries by 40-65% Child restraints:

Reduce risk of infant death by 71% and toddler death by 54%

Prevention of Road Accidents

Legislation: Speed Seat belts, Car seats, Air Bags Alcohol use Motorcycle helmets

Engineering: Restraints Safety standards

Education: Seat belts, Car seats, Air Bags Alcohol use

3. Cardiovascular Diseases

768,000 people ages 15-44 die as a result of cardiovascular disease every year

Most common causes: Ischemic heart disease (286,000 deaths) Cerebrovascular disease (159,000

deaths) Will be covered in depth in Lecture 4

4. Tuberculosis

Burden of Tuberculosis TB Pathophysiology Diagnosis of Tuberculosis Directly Observed Therapy

Burden of Tuberculosis Bacterial infection of the lungs caused by

Mycobacterium tuberculosis Bacterium infects 1 in 3 people on the planet Drugs that cure TB were discovered in 1940s Results in death in 5 years in half of cases if untreated Kills 600,000 people ages 15-44 each year Estimated that TB will kill 35 million people in next 20

years if situation does not change 2005:

8.8 million new cases (incidence) Growing 1%/year 1.6 million deaths 98% of deaths occur in developing world

Courtesy of WHO Report 2006: Global Tuberculosis Control – Surveillance, Planning, Financing

Estimated New Tuberculosis Cases in 2004

Natural History of TB Infection

Transmission Primary Tuberculosis

Latent Tuberculosis

“Reactivation”Tuberculosis

Skin-test conversion in

6-8 weeks

Spontaneous healing 6 months

Progression with concurrent HIV infection,

10% each year

Progression within 2 years,

5%

Progression after 2 years,

5%

Small PM, Fujiwara PI. Management of tuberculosis in the United States. New England Journal of Medicine. 2001 Jul 19; 345(3): 189–200.

TB Pathophysiology Primary TB Latent TB Secondary, or reactivation,

TB

TB Pathophysiology

Active TB: Symptoms

Fever Night sweats Weight loss Weakness Coughs (productive with bloody sputum)

Airborne transmission Left untreated, one person with active

TB can cough millions of infectious droplets into the air

Andrew Dandhazy, Rochester Institute of Technology.

TB Pathophysiology

TB and AIDS People with AIDS are 10x more likely to

develop active TB once infected TB is the leading cause of death among

HIV positive individuals, accounting for 13% of AIDS deaths worldwide

Diagnosis of Tuberculosis Skin test (PPD) Serum test Chest X-ray

Shows nodules in active TB

Sputum Acid-fast bacilli

CDC/Dr. Thomas Hooten.

Directly Observed Therapy (DOT)

A health care worker watches and helps as the patient swallows anti-TB medicines in his/her presence.

DOT shifts responsibility for cure from patient to health care system

Requires political commitment, accurate diagnosis, quality drugs, observation, follow up

DOT works well in many developing countries

6 month supply is $10 Cure rates of up to 95% even in

poorest countries 17 million patients worldwide have

been treated with DOT since 1995 25% of world’s population does not

have access to DOT.

Directly Observed Therapy (DOT)

Leading Causes of Mortality Ages 15-44



3. Cancer

580,000 people ages 15-44 die as a result of cancer every year

Most common causes: Liver Cancer (68,000 deaths per year) Leukemias (65,000) Stomach Cancer (58,000) Breast Cancer (57,000)

Will be covered in depth in Lecture 4

4. Self-Inflicted Injuries

Burden of Self-Inflicted Injuries Risk Factors Associated with Suicide Methods of Suicide Screening and Prevention

Burden of Self-Inflicted Injuries

480,000 people ages 15-44 take their own lives each year (4th leading cause of death)

Unipolar depressive disorder ranks #1 for DALYs in this age group in developed countries Second to HIV/AIDS in developing countries

Highest rate of completed suicides Men >65 years old

Highest rate of attempted suicides Men and women ages 20-24

Risk Factors Associated with Suicide

Psychiatric illness Affective, substance abuse, personality, other

mental disorders Other risk factors

Social adjustment problems Serious medical illness Living alone Recent bereavement Personal history of suicide attempt or

completion Divorce or separation Unemployment

Methods of Suicide

Most common: Firearms are used in 60% of suicides

2nd leading cause: Men: Hanging Women: Drug overdose or poison

Alcohol is involved in 25-40% of suicides

Women attempt suicide more often; men are more often successful

Screening and Prevention

50-66% of all suicide victims visit physician <1 month before event

10-40% in the preceding week Hard to identify who is at risk

Direct questioning has low yield General questions about sleep

disturbance, depressed mood, guilt and hopelessness

Survey instruments aren’t good at predicting what will happen


How do we quantify the efficacy of such questionnaires? Goal of screening:

Catch as many positives as possible, even at the risk of some false positives

Sensitivity: Se = probability of testing positive if you will commit

suicide

Sensitivity of best questionnaires: 56% (low)

suicidecommit who#

positive test who#Se


How many false positives result? Positive predictive value:

PPV=probability of committing suicide if you test positive

PPV of best questionnaires: 3% (pathetic)

positive test who#

suicidecommit and positive test who#PPV

Summary of Lecture 3



Lecture Three: Leading Causes of Mortality, Ages 15-44 Biomedical Engineering for Global Health.

Documents

new hiv infections

new hivaids diagnoses

new infections

hiv proteases

prevalence of hiv

unaidswhoburden of hivaids

hivaids therapyhiv

hivaids prevalence30